Role of L-type calcium channels in hippocampal neuronal network activity

This is an individual National Research Service Award for pre-doctoral research training, which provides support for promising doctoral candidates who will be performing dissertation research and training in a scientific health-related field. Autism spectrum disorder (ASD) is a pervasive but poorly understood neurological disorder. Timothy Syndrome, a disorder with a highly significant link to ASD, has recently been shown to originate from one gene with a single nucleotide substitution within the L-type calcium channel. This mutation prolongs channel opening, an effect that can be mimicked pharmacologically by the drug BayK 8644. This allows recapitulation of TS in an animal model to generate findings that can potentially generalize to other ASDs. This mouse model will allow for a detailed investigation of TS from molecular mechanisms to hippocampal circuitry. The goal of this proposal is to characterize the effects of BayK 8644 on physiological processes in the hippocampus at multiple levels from synapses to circuits and to provide a roadmap for how a single molecular malfunction can affect the functioning of a neural circuit leading to a disease phenotype.